Brain slices provide a direct access to electrically, chemically or optically probe brain function in vitro. This proposal presents a novel technology to allow multifunction, electrical and optical, assay of brain slices. The key proposed technology involves novel microfluidics system for brain slice perfusion along with the capability of simultaneously recording electrical and optical activity from brain slices. Specifically, we propose to: 1) design novel microfabricated perfusion chambers for brain slices with embedded electrodes and optical imaging capabilities, 2) carry out computational fluid dynamics, oxygen transport analysis and experimental measurements to test perfusion adequacy of the chambers, and 3) demonstrate electrical and optical transmission imaging of spreading depression in hippocampal brain slices. The proposal has been significantly revised by proposing two new designs - a) submerged microchannel chamber and b) microcapillary interface chamber - and further strengthened by improved fluidics designs and critical theoretical analysis of fluid and oxygen transport. The technology will be experimentally tested, and proof of the concept will be obtained with the help of in vitro models of spreading depression and epilepsy in hippocampal slice preparations. This project will result in a novel measurement platform for brain slice research which will facilitate basic research inquires into the study of brain's pathophysiological response in problem areas such as spreading depression, epilepsy and stroke.